Establishment of a high-throughput screening platform based on drug repurposing targeting alpha-1-acid glycoprotein and discovery of potential weight loss drugs / 药学实践杂志

Objective Alpha-1-acid glycoprotein （ORM） was a new target for the development of weight loss drugs. To search for potential weight loss drugs that could target ORM from the compound library of already marketed drugs based on drug repurposing. Methods The pGL4.20-ORM1 promoter recombinant plasmid was contructed and validated, and then a lentiviral vector was utilized to establish stable AML12 cell lines expressing ORM1 promoter-LUC-PURO. This cell line was employed for high-throughput screening of compounds from the marketed drug library, and the luminescence value of the cells was characterized by enzyme marker. Results Primary screening and secondary screening of 1 470 compounds identified 42 compounds that increased ORM1 promoter expression and could be used for further weight loss effect assessment. Conclusion This study successfully constructed LV-AML12-ORM1 promoter-LUC-PURO stable expression cell lines using lentiviral vectors, laying a foundation for efficient and stable screening of weight loss drugs targeting ORM.

A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance / 药物分析学报

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50％of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

Effect of hemopurification on acute chlorfenapyr poisoning / 中华急诊医学杂志

Objective:To evaluate the therapeutic effect of hemopurification on acute chlorfenapyr poisoning according to the blood concentration of chlorfenapyr and to provide experience for clinical treatment.Methods:Two patients who presented to our Emergency Department following an ingestion of chlorfenapyr and then were treated with hemopurification in 2022 were included. The concentrations of chlorfenapyr and its highly toxic metabolite tralopyril were dynamically monitored, and the clinical data of the patients were collected.Results:Case 1 was given hemoperfusion for the first time 13 hours after ingestion. During l hour hemoperfusion, the tralopyril decreased by 28.82%. The concentration increased and exceeded the pre-perfusion level after 2 hours of hemoperfusion. After three times of hemoperfusion, the concentrations of chlorfenapyr and tralopyril were still higher than those before the first time, reaching 248 ng/mL and 1 307 ng/mL respectively. The concentration of chlorfenapyr showed a downward trend after 130 h, and the tralopyril in blood reached the peak 3 164 ng/mL at 130 h and decreased to 2 707 ng/mL at 178 h. In case 2, the blood chlorfenapyr and tralopyril concentration was 392 ng/mL and 7 598 ng/mL respectively 150 hours after ingestion. The blood chlorfenapyr concentration decreased by 37.75% respectively after first hemoperfusion, and the tralopyril concentration decreased by 38.02% respectively. During 85 hours of continuous veno-venous hemodiafiltration (CVVHDF), the concentration of tralopyril was maintained at 4 234~6 410 ng/mL. Case 1 was followed up to 12 days and lost follow-up. Case 2 died and the survival time was 247 hours.Conclusions:Hemoperfusion can scavenge tralopyril, but CVVHDF has poor scavenging ability for tralopyril. And the apparent volume of distribution (Vd) of chlorfenapyr and tralopyril are large. After ingestion, chlorfenapyr spreads to various tissues quickly, and it is easy to accumulate in the adipose tissue. The chlorfenapyr in the tissue slowly is released back to the blood and stays in the blood for a long time. The peak concentration of chlorfenapyr appeared earlier than that of tralopyril. Clinicians should pay attention to the early removal of toxins from the digestive tract.

Analysis of epidemiology and clinical characteristics of patients with poisons purchase online / 中华急诊医学杂志

Objective:To explore the clinical characteristics of poisoned patients with poisons purchase online.Methods:A retrospective case-control study was conducted on poisoned patients purchased poisons online from 1st January 2021 to 31th May 2022 in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University. The clinical data including sex, age, way of medical treatment, cause of poisoning, exposure routes, category of toxic drugs, gastric lavage, toxic detection and prognosis of patients were collected and compared with those patients obtained poisons at stores as the control group.Results:Totally 318 poisoned patients were included in this study, of which 44 (13.8%) were obtained poisons online. Compared with the patients obtained poisons at stores, the patients obtained poisons online were younger ( P<0.001), and had higher proportion of suicide intention ( P=0.006), more oral route exposure ( P=0.029), and more proportions of receiving gastric lavage before transfer to the hospital ( P=0.001). Pesticides and fertilizers with organic heterocycles were the main types of poisons in the online group, and there was no statistical difference in the distribution of poisons compared with the control group. Mixed drug poisoning was the leading cause in both online group (27.8%) and control group (38.8%) in drug overdose poisoned types, followed by dextromethorphan (16.7%) and estazolam (15.5%) in the online group. Conclusions:Young people are the main group getting poisons through the Internet. Health education should be strengthened for this group, and online shopping platforms should pay attention to the poisoning risk of potential overdose drugs or poisons transactions.

Clinical value of sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning / 中华急诊医学杂志

Objective:To explore the clinical value of urine semi-quantitative colorimetry by sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning.Methods:The data of 49 patients with acute diquat poisoning treated in the First Affiliated Hospital of Nanjing Medical University from December 3, 2020 to November 23, 2022 were retrospectively analyzed, the correlation between urine colorimetric results and plasma diquat concentration was observed, and the predictive value of urine colorimetric results for target organ damage and prognosis were evaluated.Results:There was a significant correlation between urine colorimetric results and plasma diquat concentration, the correlation coefficient was r=0.89, P <0.01. The cut-off value of urine colorimetry for the predicting the damage of gastrointestinal tract, liver, kidney, and central nervous system injury were 2.5, 3.5, 3.5, 5.5, respectively; in which the urine colorimetric results showed the highest sensitivity in predicting digestive tract injury [ AUC 0.93 (95% CI:0.89-1.00)]. The cut-off value of urine colorimetry for the prognosis of death was 4.5, the positive predictive value was 64.2%, and the negative predictive value was 95.2%. Conclusions:The urine semi-quantitative method can be used for rapid prediction of the plasma diquat concentration range on admission. The urine colorimetry results can also effectively predict the occurrence of organ injury and clinical outcome related to diquat poisoning, which provides evidence for the clinical diagnosis and therapy.

Application of toxicant and drug detection in 895 patients with clinical poisoning diseases / 中华急诊医学杂志

Objective:To explore the diagnostic value of the toxicant and drug detection in clinical poisoning diseases and analyze the clinical characteristics of patients with positive poison test.Methods:This study was a multicenter retrospective cohort study. Sampling and clinical information data were collected between October 1, 2020 and September 30, 2022 from 41 tertiary hospitals in and around Jiangsu province. The clinical characteristics of patients with positive toxicology tests were analyzed, and the correlation between the drug sampling situation and the test results was analyzed..Results:A total of 895 patients with clinical diagnosis or suspected poisoning were enrolled in this study. Among them, 652 patients had positive results, accounting for 72.85%. Among all positive patients, 506 patients were exposed to a single poison and 147 patients were exposed to multiple poisons. The top three poisons were pesticide herbicides (202 cases, 30.98%), sedative and psychotropic drugs (151 cases, 23.16%), and pesticide insecticides (97 cases, 14.88%). Among 541 patients with clear exposure history, the positive rate was 78.19%, and among 354 patients with unclear exposure history, the positive rate was 64.69%. The top three poisons (drugs) of patients with unclear exposure history were sedative and psychotropic (82, 12.58%), herbicide (26, 3.99%), and rodenticide (22, 3.37%). Patients who admitted to hospital for unexplained consciousness disorder, abnormal blood coagulation function and multiple organ dysfunction were more likely to obtain positive poison test results.Conclusions:There is uncertainty in the exposure history of poisoning diseases, so it is necessary to improve the detection of toxic substances as soon as possible. Toxicant testing should be considered when patients have impaired consciousness, abnormal coagulation function and multiple organ dysfunction.

Effect of dexmedetomidine on TXNIP/ASK1 signaling pathway in a mouse model of intestinal ischemia-reperfusion / 中华麻醉学杂志

Objective:To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein (TXNIP)/apoptosis signal-regulated kinase 1 (ASK1) signaling pathway in a mouse model of intestinal ischemia-reperfusion (I/R).Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), TXNIP inhibitor resveratrol group (Res group) and dexmedetomidine group (Dex group). The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals. Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group, and dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group. Blood samples were collected by cardiac puncture at the end of 120-min reperfusion, then the mice were sacrificed, and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase (DAO) concentration (by enzyme-linked immunosorbent assay) and expression of TXNIP, ASK1 and cleaved-caspase-3 in small intestinal tissues (by Western blot). The apoptosis rate of intestinal epithelial cells was calculated. The intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score, serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in group Res ( P<0.05). Compared with I/R group, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in Dex group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates intestinal I/R injury may be related to inhibition of the TXNIP/ASK1 signaling pathway and reduction of cell apoptosis in mice.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project / 老年心脏病学杂志（英文版）

BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Acupuncture of revised acupoint combination around the skull base for post-stroke mild cognitive impairment: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of acupuncture of revised acupoint combination around the skull base in treating post-stroke mild cognitive impairment (PSMCI), and preliminary explore its action mechanism.@*METHODS@#A total of 76 PSMCI patients were randomly divided into an observation group (38 cases, 4 cases dropped off) and a control group (38 cases, 3 cases dropped off, 1 case was removed). In the observation group, acupuncture of revised acupoint combination around the skull base (bilateral Fengchi [GB 20], Wangu [GB 12], Tianzhu [BL 10] and Yamen [GV 15], Baihui [GV 20]) was used for treatment. In the control group, 8 non-meridian and non-acupoint points at the distal end were selected for shallow puncture treatment. Retaining the needles of 30 min, once every other day,3 times a week for 4 weeks in both groups. The scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Barthel index (BI) and serum levels of cystatin C (Cys-C) and homocysteine (Hcy) were compared in the two groups before and after treatment, and the clinical efficacy was evaluated.@*RESULTS@#After treatment, the scores of MoCA were increased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was higher than that in the control group (P<0.05). The scores of MMSE and BI were increased compared with those before treatment in the observation group (P<0.05), and the score of MMSE in the observation group was higher than that in the control group (P<0.05). After treatment, the serum levels of Cys-C and Hcy were decreased compared with those before treatment in the observation group (P<0.05), and lower than those in the control group (P<0.05). After treatment, the serum level of Cys-C was increased compared with that before treatment in the control group (P<0.05). The total effective rate of the observation group was 88.2% (30/34), which was higher than 32.4% (11/34) of the control group (P<0.05).@*CONCLUSION@#Acupuncture of revised acupoint combination around the skull base can improve cognitive function and daily living ability of PSMCI patients, which may be related to the down regulation of serum levels of Cys-C and Hcy.

Radiation environment monitoring and analysis of exempted X-ray devices / 中国辐射卫生

Objective To propose specific suggestions for exemption management of X-ray devices applying for exemption management. Methods The weight analysis of influence of shielding thickness and tube voltage on the radiation dose leakage of low-energy X-ray devices was carried out through test analysis, and the radiation status of 50 X-ray devices applied for end-user exemption in Shenzhen, China was investigated. Results There was no significant correlation between the ambient dose equivalent rate and the tube voltage and tube current of the X-ray device. The ambient dose equivalent rate of 50 X-ray devices was 0.16-1.20 μSv/h. Among them, 8 X-ray devices had radiation dose leakage, that is, the ambient dose equivalent rate was greater than 0.36 μSv/h; the ambient dose equivalent rate of one X-ray device was 1.2 μSv/h, exceeding exemption management requirements. Conclusion Applications for exemption management and filing of X-ray devices should be treated differently, and their own shielding effect and inherent safety have a greater impact on radiation safety, which should be focused on.

Non-Contrast Cine Cardiac Magnetic Resonance Derived-Radiomics for the Prediction of Left Ventricular Adverse Remodeling in Patients With ST-Segment Elevation Myocardial Infarction

Objective@#To investigate the predictive value of radiomics features based on cardiac magnetic resonance (CMR) cine images for left ventricular adverse remodeling (LVAR) after acute ST-segment elevation myocardial infarction (STEMI). @*Materials and Methods@#We conducted a retrospective, single-center, cohort study involving 244 patients (random-split into 170 and 74 for training and testing, respectively) having an acute STEMI (88.5% males, 57.0 ± 10.3 years of age) who underwent CMR examination at one week and six months after percutaneous coronary intervention. LVAR was defined as a 20% increase in left ventricular end-diastolic volume 6 months after acute STEMI. Radiomics features were extracted from the oneweek CMR cine images using the least absolute shrinkage and selection operator regression (LASSO) analysis. The predictive performance of the selected features was evaluated using receiver operating characteristic curve analysis and the area under the curve (AUC). @*Results@#Nine radiomics features with non-zero coefficients were included in the LASSO regression of the radiomics score (RAD score). Infarct size (odds ratio [OR]: 1.04 (1.00–1.07); P = 0.031) and RAD score (OR: 3.43 (2.34–5.28); P < 0.001) were independent predictors of LVAR. The RAD score predicted LVAR, with an AUC (95% confidence interval [CI]) of 0.82 (0.75–0.89) in the training set and 0.75 (0.62–0.89) in the testing set. Combining the RAD score with infarct size yielded favorable performance in predicting LVAR, with an AUC of 0.84 (0.72–0.95). Moreover, the addition of the RAD score to the left ventricular ejection fraction (LVEF) significantly increased the AUC from 0.68 (0.52–0.84) to 0.82 (0.70–0.93) (P = 0.018), which was also comparable to the prediction provided by the combined microvascular obstruction, infarct size, and LVEF with an AUC of 0.79 (0.65–0.94) (P = 0.727). @*Conclusion@#Radiomics analysis using non-contrast cine CMR can predict LVAR after STEMI independently and incrementally to LVEF and may provide an alternative to traditional CMR parameters.

Study on the fingerprint of total saponins from Mussaenda pubescens and the spectrum-effect relationship of its hepatoprotective activity / 中国药房

OBJECTIVE To establish the fingerprint of total saponins from Mussaenda pubescens， and to study the spectrum- effect relationship of its hepatoprotective activity. METHODS Ten batches of total saponins from M. pubescens from different origins were prepared using 75% ethanol as solvent. High-performance liquid chromatography （HPLC） and the Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition） were used to draw the fingerprints of 10 batches of total saponins from M. pubescens. The similarity evaluation and identification of common peaks were conducted. The same HPLC method was adopted to determine the contents of five triterpenoid saponins （mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G and mussaendoside O）. The hepatoprotective effect of total saponins from M. pubescens was investigated by establishing carbon tetrachloride-induced acute liver injury model mice， and the spectrum-effect relationship was studied by using grey correlation analysis. RESULTS There were 11 common peaks in 10 batches of total saponins from M. pubescens， 5 of which were identified， i.e. mussaendoside H （peak 3）， mussaendoside U （peak 7）， mussaglaoside C （peak 8）， mussaendoside G （peak 9） and mussaendoside O （peak 11）； the similarities of 10 batches of samples ranged 0.940- 0.991. Average contents of mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G， mussaendoside O were 0.01- 0.05， 0.10-0.21， 0.10-0.18， 0.03-0.08， 0.20-0.40 mg/g， respectively. Ten batches of total saponins from M. pubescens could generally reduce the contents of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， and tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in liver tissue of model mice （P＜0.05 or P＜0.01）. The E-mail：13878195336@139.com correlation between the common peak areas and the contents of ALT， AST， TNF-α， IL-6 and IL-1β were 0.602-0.757， 0.585-0.833， 0.593-0.795， 0.618-0.820， 0.607-0.804， respectively； the peaks with high correlation were peaks 11， 9 and 8 in order. CONCLUSIONS Ten batches of total saponins from M. pubescens have similar components， and the average contents of mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G and mussaendoside O are different. The batches of samples have a certain degree of hepatoprotective effect； mussaendoside O， mussaendoside G and mussaglaoside C may be its main active components.

18F-FDG PET/CT Prognostic Role in Diffuse Large B-cell Lymphoma Following Chemotherapy / 中山大学学报(医学科学版)

ObjectiveTo assess the prognostic value of 18F-FDG PET/CT parameters for predicting therapeutic response in diffuse large B-cell lymphoma （DLBCL）. MethodsWe retrospectively analyzed the clinical data and 18F-FDG PET/CT radiomics features of 81 DLBCL patients enrolled between June 2015 and October 2020. Multivariate logistic regression analysis was used to identify the predictive factors for therapeutic response of DLBCL， based on which a predictive model was developed accordingly. The performance of the model was evaluated by receiver operating characteristic （ROC） curves and calibration plots. ResultsDuring the two years after first chemotherapy， 23 patients （28.3%） developed relapse and 58 patients （71.7%） had progression-free survival （PFS）. The analysis for the predictive capability of the binary logistic regression model incorporating the PET/CT features revealed that the imaging features of 18F-FDG PET/CT after chemotherapy were independent prognostic factors for PFS. Among them， SUVTHR-mean2 was the most important factor for predicting therapeutic response in DLBCL patients after chemotherapy， with a cutoff value of 2.00 （AUC=0.81）. Conclusions18F-FDG PET/CT showed a valuable prognostic performance for PFS in DLBCL patients after chemotherapy， with the imaging feature after chemotherapy SUVTLR-mean2 being the optimal independent predictor. Our predictive model of imaging features might have an important prognostic value in assessing the risk of disease progression， guiding the treatment and follow-up protocol， improving therapeutic efficiency and cutting down the medical cost.

Advances in potential drugs for improvement of energy metabolism in heart failure / 药学实践杂志

Heart failure (HF) is a global public health problem with high morbidity and mortality. Numerous studies have shown that HF is caused by severe disturbance of energy metabolism, resulting in insufficient cardiac energy supply. This lack of energy could lead to a failure of the heart to pump blood and a failure of energy metabolism in other organs throughout the body. Currently, therapeutics of HF work by reducing heart rate and cardiac preload and afterload, symptomatic treatment, or delaying the progression of the disease. However, drugs targeting heart energy metabolism have not been developed. the main characteristics of cardiac energy metabolism, metabolic changes during HF were summarized and drugs that improve cardiac function through energy metabolism were discussed, which could provide a new research direction for the development and application of drugs in treatment of heart failure.

Research progress of nuclear factor erythroid 2-related factor 2 in pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a common chronic interstitial lung disease. It is characterized by excessive deposition of extracellular matrix and remodeling of lung tissue structure, resulting in severe impairment of lung function. The cause of its pathogenesis is still unclear. Therefore, it is urgent to explore its pathogenesis and find new targets to combat pulmonary fibrosis. Studies have shown that nuclear factor erythroid 2-related factor 2 can maintain the body's redox homeostasis by regulating antioxidant genes and combining antioxidant response components, thereby protecting tissues and cells from oxidative stress. In recent years, many studies have proved that nuclear factor erythroid 2 -related factor 2 can play an anti-fibrotic role by alleviating oxidative stress, inhibiting macrophage polarization, activating autophagy, inhibiting ferroptosis, and blocking epithelial-mesenchymal transition. This paper provides a brief review of the association and research progress of nuclear factor erythroid 2-related factor 2 with pulmonary fibrosis, with the aim of providing a new direction for the precise treatment of pulmonary fibrosis.

Research progress of metformin in the pathogenesis of pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a chronic, progressive and irreversible respiratory disease characterized by hyperposition of extracellular matrix leading to inflammation and extensive lung remodeling. There is currently no effective treatment. Multiple studies have shown that metformin is a classic antiglycemic drug with antifibrotic potential. However, at present, there is no consensus on the specific mechanism of metformin's anti-fibrosis effect, and this paper reviews the research progress of metformin in the field of pulmonary fibrosis in recent years, mainly from IGF-1/IGF-1R/PI3K signaling, AMPK/mTOR signaling, TGF-β/Smad signaling pathway, and intervening in myofibroblast proliferation and apoptosis, improving oxidative stress, inhibiting epithelial interstitial transformation and transglutaminase. In order to be able to more deeply and comprehensively understand the antifibrosis mechanism and clinical application scope of metformin in the future, and provide new ideas for the treatment of pulmonary fibrosis.

Effectss of hyperoside on traumatic brain injury rats by regulating RhoA/ROCK signaling pathway / 中国临床药理学与治疗学

AIM: To investigate the effects of hyperoside on traumatic brain injury (TBI) rats by regulating the Ras homolog gene family, member A (RhoA)/Rho-associated coiled coil-forming kinase (ROCK) signal pathway. METHODS: The TBI rat model was established by modified Feeney free fall hit method, and was randomly divided into model group, low-dose hyperoside (60 mg / kg) group, high-dose hyperoside (120 mg / kg) group, high-dose hyperoside (120 mg / kg) + no load group, and high-dose hyperoside (120 mg / kg) + RhoA overexpression group, with 10 rats in each group, another 10 healthy rats were set as sham operation group, after hyperoside and plasmid were grouped, the nerve injury was detected by modified neurological deficit score (mNSS) and dark avoidance test; Evans blue (EB) quantitative method was used to detect the permeability of blood brain barrier in rats; ultrastructural damage of blood-brain barrier was observed by transmission electron microscopy; the levels of tumor necrosis factor- α (TNF- α), interleukin-8 (IL-8), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and brain tissue of rats were measured with the kit; and the expression of RhoA/ROCK pathway related proteins in rat brain was detected by Western blot. RESULTS: Compared with the sham operation group, the blood brain barrier structure of the model group rats was damaged, the step-through latency and SOD level decreased obviously (P0.05). CONCLUSION: Hyperoside can inhibit neuroinflammation and oxidative stress in TBI rats by down-regulating RhoA / ROCK signal pathway, thereby reducing the damage of blood brain barrier and repairing its neural function.

Research progress in sodium calcium exchanger and heart failure with preserved ejection fraction / 中国临床药理学与治疗学

Sodium calcium exchanger (NCX) is encoded by the SCL8 family genes and belongs to the cation/Ca

Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling / 中国结合医学杂志

OBJECTIVE@#To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.@*METHODS@#Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.@*RESULTS@#High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFβ R1, TGFβ R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01).@*CONCLUSIONS@#Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.